Phosphorus pentachloride → benzhydryl (6R)-3-(chloromethyl)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 615788Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 615788
[C:1]([O:5][C:6]([CH2:8][O:9]/[N:10]=[C:11](/[C:15]1[N:16]=[C:17]([NH:20][C:21]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[S:18][CH:19]=1)\[C:12](O)=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].P(Cl)(Cl)(Cl)(Cl)Cl.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.Cl.[NH2:59][CH:60]1[C:85](=[O:86])[N:62]2[C:63]([C:69]([O:71][CH:72]([C:79]3[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=3)[C:73]3[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=3)=[O:70])=[C:64]([CH2:67][Cl:68])[CH2:65][S:66][C@H:61]12>C(Cl)Cl.C(OCC)(=O)C>[C:1]([O:5][C:6]([CH2:8][O:9]/[N:10]=[C:11](/[C:15]1[N:16]=[C:17]([NH:20][C:21]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[S:18][CH:19]=1)\[C:12]([NH:59][CH:60]1[C:85](=[O:86])[N:62]2[C:63]([C:69]([O:71][CH:72]([C:73]3[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=3)[C:79]3[CH:80]=[CH:81][CH:82]=[CH:83][CH:84]=3)=[O:70])=[C:64]([CH2:67][Cl:68])[CH2:65][S:66][C@H:61]12)=[O:13])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

7

Edukt 4

HCID 24819Phosphorus pentachlorideHCID 11708267BistrimethylsilylacetamidHCID 13078701(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acidHCID 13239629Benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride

Produkt 1

HCID 87882460benzhydryl (6R)-3-(chloromethyl)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To an ice-cooled solution of (Z)-2-t-butoxycarbonylmethoxyimino-2-(tritylaminothiazol-4-yl)acetic acid (IVg') (2.71 g, 5 mmoles) in CH2Cl2 (20 ml) was added PCl5 (1.24 g, 6 mmoles), and the solution was stirred for 20 minutes at room temperature. The acid chloride solution was added under ice-cooling to a solution of the silylated 7-ACA ester, which was prepared by adding bis(trimethylsilyl)acetamide (BSA, 3.7 ml, 15 mmoles) to a stirred suspension of benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride (V) (2.25 g, 5 mmoles) in CH2Cl2 (20 ml). The reaction mixture was stirred at room temperature for 30 minutes, diluted with ethyl acetate (200 ml) and washed with an aqueous NaHCO3 solution and water. After drying over Na2SO4, the solution was evaporated and the residue was purified by silica gel chromatography (Wako gel C-200, 60 g). The desired fractions, eluted by CHCl3, were combined and concentrated to give 3.16 g (67%) of the title compound VIg'.

Aufarbeitung

  1. customwas prepared
  2. stirringThe reaction mixture was stirred at room temperature for 30 minutes
  3. washwashed with an aqueous NaHCO3 solution and water
  4. dry with materialAfter drying over Na2SO4
  5. customthe solution was evaporated
  6. customthe residue was purified by silica gel chromatography (Wako gel C-200, 60 g)
  7. washThe desired fractions, eluted by CHCl3
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-800dadbfc4c644ffaa50a81b9f94575e
Quelldatensatz
uspto-grants-1985_02
Patentnummer
US04500526

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